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WO2011117289A1 - Dérivés de chromén-2-one et leur utilisation à titre d'inhibiteurs de recaptage des neurotransmetteurs monoaminés - Google Patents

Dérivés de chromén-2-one et leur utilisation à titre d'inhibiteurs de recaptage des neurotransmetteurs monoaminés Download PDF

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Publication number
WO2011117289A1
WO2011117289A1 PCT/EP2011/054431 EP2011054431W WO2011117289A1 WO 2011117289 A1 WO2011117289 A1 WO 2011117289A1 EP 2011054431 W EP2011054431 W EP 2011054431W WO 2011117289 A1 WO2011117289 A1 WO 2011117289A1
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WIPO (PCT)
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disorder
pharmaceutically acceptable
compound
compound according
methyl
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PCT/EP2011/054431
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English (en)
Inventor
Dan Peters
Gordon Munro
Elsebet Østergaard NIELSEN
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Neurosearch A/S
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Publication of WO2011117289A1 publication Critical patent/WO2011117289A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • This invention relates to novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen-2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors.
  • the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
  • Serotonin Selective Reuptake Inhibitors currently provide efficacy in the treatment of several CNS disorders, including depression and panic disorder.
  • SSRIs are generally perceived by psychiatrists and primary care physicians as effective, well- tolerated and easily administered. However, they are associated with a number of undesirable features.
  • WO 2006/035034 (NeuroSearch A/S)
  • WO 2007/093604 (NeuroSearch A/S)
  • chromen-2-one derivatives useful as monoamine neurotransmitter reuptake inhibitors.
  • the invention provides a compound of Formula (I):
  • R 1 and R 2 are as defined below.
  • the invention provides a pharmaceutical composition, comprising a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.
  • the invention provides the use of a compound of the invention, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or a disorder or a condition of a mammal, including a human, which disease, disorder or condition is responsive to inhibition of monoamine neurotransmitter re-uptake in the central nervous system.
  • the invention in another aspect, relates to a method for treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disorder, disease or condition is responsive to responsive to inhibition of monoamine neurotransmitter re-uptake in the central nervous system, which method comprises the step of administering to such a living animal body in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof.
  • Another embodiment of the invention is the provision of compounds with optimal pharmacodynamic and/or pharmacokinetic properties such as kinetic behavior, bioavailability, solubility, efficacy and/or adverse effects.
  • the present invention provides compounds of Formula (I)
  • R 1 represents Ci-6-alkyl and R 2 represents methyl or methoxy.
  • R 2 represents methyl. In another embodiment, R 2 represents methoxy.
  • R 1 represents Ci-3-alkyl. In a special embodiment, R 1 represents methyl.
  • the compound of the invention is:
  • Ci-6-alkyl as used herein means a saturated, branched or straight hydrocarbon group having from 1 -6 carbon atoms, e.g. Ci-3-alkyl, Ci -4 -alkyl, C h alky!, C2-6-alkyl, C3-6-alkyl, and the like.
  • Representative examples are methyl, ethyl, propyl (e.g. prop-1 -yl, prop-2-yl (or /so-propyl)), butyl (e.g. 2-methylprop-2-yl (or tert- butyl), but-1 -yl, but-2-yl), pentyl (e.g. pent-1 -yl, pent-2-yl, pent-3-yl), 2-methylbut-1 -yl, 3-methylbut-1 -yl, hexyl (e.g. hex-1 -yl), and the like.
  • treatment means the management and care of a patient for the purpose of combating a disease, disorder or condition.
  • the term is intended to include the delaying of the progression of the disease, disorder or condition, the alleviation or relief of symptoms and complications, and/or the cure or elimination of the disease, disorder or condition.
  • the patient to be treated is preferably a mammal, in particular a human being.
  • medicament means a pharmaceutical composition suitable for administration of the pharmaceutically active compound to a patient.
  • pharmaceutically acceptable means suited for normal pharmaceutical applications, i.e. giving rise to no adverse events in patients etc.
  • an effective amount means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment.
  • terapéuticaally effective amount of a compound as used herein means an amount sufficient to cure, alleviate or partially arrest the clinical manifestations of a given disease and its complications. An amount adequate to accomplish this is defined as “therapeutically effective amount”. Effective amounts for each purpose will depend on the severity of the disease or injury as well as the weight and general state of the subject. It will be understood that determining an appropriate dosage may be achieved using routine experimentation, by constructing a matrix of values and testing different points in the matrix, which is all within the ordinary skills of a trained physician or veterinary.
  • the compound of the invention may be provided in any form suitable for the intended administration. Suitable forms include pharmaceutically (i.e. physiologically) acceptable salts, and pre- or prodrug forms of the compound of the invention.
  • Examples of pharmaceutically acceptable addition salts include, without limitation, the non-toxic inorganic and organic acid addition salts such as the hydro- chloride, the hydrobromide, the nitrate, the perchlorate, the phosphate, the sulphate, the formate, the acetate, the aconate, the ascorbate, the benzenesulphonate, the benzoate, the cinnamate, the citrate, the embonate, the enantate, the fumarate, the glutamate, the glycolate, the lactate, the maleate, the malonate, the mandelate, the methanesulphonate, the naphthalene-2-sulphonate, the phthalate, the salicylate, the sorbate, the stearate, the succinate, the tartrate, the toluene-p-sulphonate, and the like.
  • Such salts may be formed by procedures well known and described in the art.
  • Examples of pharmaceutically acceptable cationic salts of a compound of the invention include, without limitation, the sodium, the potassium, the calcium, the mag- nesium, the zinc, the aluminium, the lithium, the choline, the lysinium, and the ammonium salt, and the like, of a compound of the invention containing an anionic group.
  • Such cationic salts may be formed by procedures well known and described in the art.
  • onium salts of N-containing compounds are also contemplated as pharmaceutically acceptable salts.
  • Preferred “onium salts” include- de the alkyl-onium salts, the cycloalkyl-onium salts, and the cycloalkylalkyl-oniunn salts.
  • pre- or prodrug forms of the compound of the invention include examples of suitable prodrugs of the substances according to the invention include compounds modified at one or more reactive or derivatizable groups of the parent compound. Of interest are compounds modified at a carboxyl group, a hydroxyl group, or an amino group. Examples of suitable derivatives are esters or amides.
  • the compound of the invention may be provided in dissoluble or indissoluble forms together with a pharmaceutically acceptable solvent such as water, ethanol, and the like.
  • Dissoluble forms may also include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate, and the like. In general, the dissoluble forms are considered equivalent to indissoluble forms for the purposes of this invention.
  • the compounds of the invention may be used in their labelled or unlabelled form.
  • the labelled compound has one or more atoms replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature.
  • the labelling will allow easy quantitative detection of said compound.
  • the labelled compounds of the invention may be useful as diagnostic tools, radio tracers, or monitoring agents in various diagnostic methods, and for in vivo receptor imaging.
  • the labelled isomer of the invention preferably contains at least one radionuclide as a label. Positron emitting radionuclides are all candidates for usage. In the context of this invention the radionuclide is preferably selected from 2 H (deuterium), 3 H (tritium), 11 C, 13 C, and 14 C.
  • the physical method for detecting the labelled isomer of the present invention may be selected from Position Emission Tomography (PET), Single Photon Imaging Computed Tomography (SPECT), Magnetic Resonance Spectroscopy (MRS), Magnetic Resonance Imaging (MRI), and Computed Axial X-ray Tomography (CAT), or combinations thereof.
  • PET Position Emission Tomography
  • SPECT Single Photon Imaging Computed Tomography
  • MRS Magnetic Resonance Spectroscopy
  • MRI Magnetic Resonance Imaging
  • CAT Computed Axial X-ray Tomography
  • the compounds of the invention may be prepared by conventional methods for chemical synthesis, e.g. those described in the working examples.
  • the starting materials for the processes described in the present application are known or may readily be prepared by conventional methods from commercially available chemicals.
  • one compound of the invention can be converted to another compound of the invention using conventional methods.
  • the end products of the reactions described herein may be isolated by conventional techniques, e.g. by extraction, crystallisation, distillation, chromatography, etc.
  • Compounds of the invention may be tested for their ability to inhibit reuptake of the monoamines dopamine, noradrenaline and serotonin in synaptosomes e.g. such as described in WO 97/30997 (NeuroSearch A/S) or WO 97/16451 (NeuroSearch A/S). Based on the balanced activity observed in these tests the compound of the invention is considered useful for the treatment, prevention or alleviation of a disease or a disorder or a condition of a mammal, including a human, which disease, disorder or condition is responsive to inhibition of monoamine neurotransmitter re-uptake in the central nervous system.
  • the compounds of the invention are considered useful for the treatment, prevention or alleviation of: mood disorder, depression, atypical depres- sion, depression secondary to pain, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar I disorder, bipolar II disorder, cyclothymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, pseudode- mentia, Ganser's syndrome, obsessive compulsive disorder, panic disorder, panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without his- tory of panic disorder, panic attack, memory deficits, memory loss, attention deficit hyperactivity disorder (ADHD), obesity, anxiety, generalized anxiety disorder, eating disorder, Parkinson's disease, parkinsonism, dementia, dementia of ageing, senile dementia, Alzheimer's disease, Down's syndrome, acquired immunodeficiency syndrome dementia complex, memory dysfunction in ageing, specific phobia, social phobia, so- cial anxiety disorder, post-traumatic stress disorder, acute stress disorder, drug
  • the compounds of the invention are considered useful for the treatment or alleviation of pain, e.g. acute pain, chronic pain, mild pain, moderate or severe pain, postoperative pain, neuropathic pain, central neuropathic pain, pain related to diabetic neuropathy, to postherpetic neuralgia, to peripheral nerve injury, to phantom limb pain, to fibromyalgia, to chronic regional pain syndrome, somatic pain, visceral pain or cutaneous pain, pain caused by inflammation or by infection, pain re- lated to osteoarthritis, rheumatoid arthritis, neuronal hyperexcitability disorders, peripheral nerve hyperexcitability, chronic headache, migraine, migraine-related disorders or tension-type headache.
  • pain e.g. acute pain, chronic pain, mild pain, moderate or severe pain, postoperative pain, neuropathic pain, central neuropathic pain, pain related to diabetic neuropathy, to postherpetic neuralgia, to peripheral nerve injury, to phantom limb pain, to fibromyalg
  • the compounds of the invention are considered useful for the treatment or alleviation of pain. In another embodiment, the compounds of the invention are considered useful for the treatment or alle- viation of depression. In another embodiment, the compounds of the invention are considered useful for the treatment or alleviation of attention deficit hyperactivity disorder (ADHD).
  • ADHD attention deficit hyperactivity disorder
  • a suitable dosage of the active pharmaceutical ingredient is within the range of from about 0.1 to about 1000 mg API per day, more preferred of from about 10 to about 500 mg API per day, most preferred of from about 30 to about 100 mg API per day, dependent, however, upon the exact mode of administration, the form in which it is administered, the indication considered, the subject and in particular the body weight of the subject involved, and further the preference and experience of the physician or veterinarian in charge.
  • Preferred compounds of the invention show a biological activity in the sub- micromolar and micromolar range, i.e. of from below 1 to about 100 ⁇ .
  • the invention provides novel pharmaceutical compositions comprising a therapeutically effective amount of the compound of the invention.
  • a compound of the invention for use in therapy may be administered in the form of the raw chemical compound, it is preferred to introduce the active ingredient, optionally in the form of a physiologically acceptable salt, in a pharmaceutical composition together with one or more adjuvants, excipients, carriers, buffers, diluents, and/or other customary pharmaceutical auxiliaries.
  • the invention provides pharmaceutical compositions comprising the compound of the invention, or a pharmaceutically acceptable salt or derivative thereof, together with one or more pharmaceutically acceptable carriers, and, op- tionally, other therapeutic and/or prophylactic ingredients, known and used in the art.
  • the carrier(s) must be "acceptable” in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof.
  • compositions of the invention may be those suitable for oral, rectal, bronchial, nasal, pulmonal, topical (including buccal and sub-lingual), transder- mal, vaginal or parenteral (including cutaneous, subcutaneous, intramuscular, intraperitoneal, intravenous, intraarterial, intracerebral, intraocular injection or infusion) administration, or those in a form suitable for administration by inhalation or insufflation, including powders and liquid aerosol administration, or by sustained release systems.
  • sustained release systems include semipermeable matrices of solid hydrophobic polymers containing the compound of the invention, which matrices may be in form of shaped articles, e.g. films or microcapsules.
  • compositions and unit dosages thereof may thus be placed into the form of pharmaceutical compositions and unit dosages thereof.
  • forms include solids, and in particular tablets, filled capsules, powder and pellet forms, and liquids, in particular aqueous or non-aqueous solutions, suspensions, emulsions, elixirs, and capsules filled with the same, all for oral use, suppositories for rectal administration, and sterile injectable solutions for parenteral use.
  • Such pharmaceutical compositions and unit dosage forms thereof may comprise conventional ingredients in conventional proportions, with or without additional active compounds or principles, and such unit dosage forms may contain any suitable effective amount of the active ingredient commensurate with the intended daily dosage range to be employed.
  • the compound of the invention can be administered in a wide variety of oral and parenteral dosage forms. It will be obvious to those skilled in the art that the following dosage forms may comprise, as the active component, either a compound of the invention or a pharmaceutically acceptable salt of a compound of the invention.
  • pharmaceutically acceptable carriers can be either solid or liquid.
  • Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dis- persible granules.
  • a solid carrier can be one or more substances which may also act as diluents, flavouring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
  • the carrier is a finely divided solid, which is in a mixture with the finely divided active component.
  • the active component is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets may contain from five or ten to about seventy percent of the active compound.
  • Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, cellulose, starch, gelatin, tragacanth, me- thylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like.
  • the term "preparation" is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component, with or without carriers, is surrounded by a carrier, which is thus in asso- ciation with it.
  • cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid forms suitable for oral administration.
  • a low melting wax such as a mixture of fatty acid glyceride or cocoa butter
  • the active component is dispersed homo- geneously therein, as by stirring.
  • the molten homogenous mixture is then poured into convenient sized moulds, allowed to cool, and thereby to solidify.
  • compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such carriers as are known in the art to be appropriate.
  • Liquid preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions.
  • parenteral injection liquid preparations can be formulated as solutions in aqueous polyethylene glycol solution.
  • the compound according to the present invention may thus be formulated for parenteral administration (e.g. by injection, for example bolus injection or continuous infusion) and may be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative.
  • the compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulation agents such as suspending, stabilising and/or dispersing agents.
  • the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.
  • Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavours, stabilising and thickening agents, as desired.
  • Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well known suspending agents.
  • viscous material such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well known suspending agents.
  • solid form preparations intended for conversion shortly before use to liquid form preparations for oral administration.
  • liquid forms include solutions, suspensions, and emulsions.
  • preparations may comprise colorants, flavours, stabilisers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.
  • the compound of the invention may be formulated as ointments, creams or lotions, or as a transdermal patch.
  • Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents.
  • Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilising agents, dispersing agents, suspending agents, thickening agents, or colouring agents.
  • compositions suitable for topical administration in the mouth include lozenges comprising the active agent in a flavoured base, usually sucrose and acacia or traga- canth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerine or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
  • Solutions or suspensions are applied directly to the nasal cavity by conventional means, for example with a dropper, pipette or spray.
  • the compositions may be provided in single or multi-dose form. In the latter case of a dropper or pipette, this may be achieved by the patient administering an appropriate, predetermined volume of the solution or suspension. In the case of a spray, this may be achieved for example by means of a metering atomising spray pump.
  • Administration to the respiratory tract may also be achieved by means of an aerosol formulation in which the active ingredient is provided in a pressurised pack with a suitable propellant such as a chlorofluorocarbon (CFC) for example dichlorodi- fluoromethane, trichlorofluoromethane, or dichlorotetrafluoroethane, carbon dioxide, or other suitable gas.
  • a suitable propellant such as a chlorofluorocarbon (CFC) for example dichlorodi- fluoromethane, trichlorofluoromethane, or dichlorotetrafluoroethane, carbon dioxide, or other suitable gas.
  • CFC chlorofluorocarbon
  • the aerosol may conveniently also contain a surfactant such as lecithin.
  • the dose of drug may be controlled by provision of a metered valve.
  • the active ingredients may be provided in the form of a dry powder, for example a powder mix of the compound in a suitable powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP).
  • a powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP).
  • PVP polyvinylpyrrolidone
  • the powder carrier will form a gel in the nasal cavity.
  • the powder composition may be presented in unit dose form for example in capsules or cartridges of, e.g., gelatin, or blister packs from which the powder may be administered by means of an inhaler.
  • the compound In compositions intended for administration to the respiratory tract, including intranasal compositions, the compound will generally have a small particle size for ex- ample of the order of 5 microns or less. Such a particle size may be obtained by means known in the art, for example by micron ization.
  • compositions adapted to give sustained release of the active ingredient may be employed.
  • the pharmaceutical preparations are preferably in unit dosage forms.
  • the preparation is subdivided into unit doses containing appropriate quantities of the active component.
  • the unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packaged tablets, capsules, and powders in vials or ampoules.
  • the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in pack- aged form.
  • the invention provides tablets or capsules for oral administration.
  • the invention provides liquids for intravenous administration and continuous infusion.
  • the dose administered must of course be carefully adjusted to the age, weight and condition of the individual being treated, as well as the route of administration, do- sage form and regimen, and the result desired, and the exact dosage should of course be determined by the practitioner.
  • compositions containing of from about 0.1 to about 500 mg of active ingredient per individual dose, preferably of from about 1 to about 100 mg, most preferred of from about 1 to about 10 mg, are suitable for therapeutic treatments.
  • the active ingredient may be administered in one or several doses per day.
  • a satisfactory result can, in certain instances, be obtained at a dosage as low as 0.1 ⁇ g kg i.v. and 1 ⁇ g kg p.o.
  • the upper limit of the dosage range is presently considered to be about 10 mg/kg i.v. and 100 mg/kg p.o. Ranges are from about 0.1 ⁇ g kg to about 10 mg/kg/day i.v., and from about 1 ⁇ g kg to about 100 mg/kg/day p.o.
  • the invention provides a method for the treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disease, disorder or condition is responsive to inhibition of monoamine neurotransmitter re-uptake in the central nervous system, and which method comprises administering to such a living animal body, including a human, in need thereof an effective amount of a compound of the invention.
  • suitable dosage ranges are 0.1 to 1000 mil I i- grams daily, 10-500 milligrams daily, and especially 30-100 milligrams daily, dependent as usual upon the exact mode of administration, form in which administered, the indication toward which the administration is directed, the subject involved and the body weight of the subject involved, and further the preference and experience of the physician or veterinarian in charge.
  • Triphenylphosphine (3.53 g, 13.46 mmol) was solved in toluene (40 ml) and cooled to ⁇ 20°C.
  • Diethylazodicarboxylate (40% in toluene) (6.0 ml, 13.09 mmol) was added to the mixture below 20°C, followed by stirring for 10 minutes.
  • Tropine (1 .6 g, 1 1 .3 mmol) was added and after 10 minutes, 7-hydroxy-3-methyl-chromen-2-one (2.0 g, 1 1 .3 mmol) was added to the mixture.
  • the temperature raised to 32°C due to an exothermic reaction and adopts a red colour.
  • the mixture precipitated.
  • the mixture was allowed to stir for 70 h at room temperature.
  • the compound was tested for its ability to inhibit the reuptake of the monoamine neurotransmitters dopamine (DA) noradrenaline (NA) and serotonine (5-HT) in synaptosomes as described in WO 97/16451 .
  • DA dopamine
  • NA noradrenaline
  • 5-HT serotonine
  • test values are given as IC 5 o (the concentration ( ⁇ ) of the test substance which inhibits the specific binding of ⁇ -DA, ⁇ - ⁇ , or ⁇ -5- ⁇ by 50%).

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  • Bioinformatics & Cheminformatics (AREA)
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  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

Les présentes demandes de brevet concernent de nouveaux dérivés de 8-aza-bicyclo[3.2.1]oct-3-yloxy)- chromén-2-one et leur utilisation à titre d'inhibiteurs de recaptage des neurotransmetteurs monoaminés. Selon d'autres aspects, les présentes demandes de brevet concernent l'utilisation de ces composés dans une méthode thérapeutique et des compositions pharmaceutiques contenant les composés selon l'invention.
PCT/EP2011/054431 2010-03-25 2011-03-23 Dérivés de chromén-2-one et leur utilisation à titre d'inhibiteurs de recaptage des neurotransmetteurs monoaminés WO2011117289A1 (fr)

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DKPA201000247 2010-03-25
US31908110P 2010-03-30 2010-03-30
US61/319,081 2010-03-30

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8697721B2 (en) 2009-05-15 2014-04-15 Aniona Aps Chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016451A1 (fr) 1995-11-02 1997-05-09 Neurosearch A/S Derives tropane condenses en tant qu'inhibiteurs de recaptage des neurotransmetteurs
WO1997030997A1 (fr) 1996-02-22 1997-08-28 Neurosearch A/S Derives du tropane, leur preparation et utilisation
WO2006035034A1 (fr) 2004-09-30 2006-04-06 Neurosearch A/S Nouveaux derives de chromene-2-one et leur utilisation comme inhibiteurs de recapture du neurotransmetteur monoamine
WO2007093604A1 (fr) 2006-02-17 2007-08-23 Neurosearch A/S Nouveaux dérivés de chromen-2-one et leurs utilisation en tant qu'inhibiteurs de recaptage d'un neuro-transmetteur monoamine

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016451A1 (fr) 1995-11-02 1997-05-09 Neurosearch A/S Derives tropane condenses en tant qu'inhibiteurs de recaptage des neurotransmetteurs
WO1997030997A1 (fr) 1996-02-22 1997-08-28 Neurosearch A/S Derives du tropane, leur preparation et utilisation
WO2006035034A1 (fr) 2004-09-30 2006-04-06 Neurosearch A/S Nouveaux derives de chromene-2-one et leur utilisation comme inhibiteurs de recapture du neurotransmetteur monoamine
WO2007093604A1 (fr) 2006-02-17 2007-08-23 Neurosearch A/S Nouveaux dérivés de chromen-2-one et leurs utilisation en tant qu'inhibiteurs de recaptage d'un neuro-transmetteur monoamine

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* Cited by examiner, † Cited by third party
Title
"Reminqton's Pharmaceutical Sciences", MAACK PUBLISHING CO.

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8697721B2 (en) 2009-05-15 2014-04-15 Aniona Aps Chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

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